Evidence map›Paper›PMID 42386761›Full record

ArticleNature communications2026

Pre-existing antibody and T cell responses to SaCas9, AsCas12a and CasΦ are comparable in naïve individuals.

Vijaya L Simhadri, Pratima Bajgain, Sharon Vijayanand, Wojciech Jankowski, Atul Rawal, Lauren Thijs, Thomas Van Doninck, Kurt Boonen, Sofie Pattyn, Elise Pepermans and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Vijaya L SimhadriDivision of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID 0000-0002-3177-5250
Pratima BajgainDivision of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID 0000-0001-6483-7369
Sharon VijayanandDivision of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Wojciech JankowskiDivision of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID 0000-0002-7000-9057
Atul RawalDivision of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID 0000-0003-3443-693X
Lauren ThijsImmuneSpec, Niel, Belgium.
Thomas Van DoninckImmuneSpec, Niel, Belgium.
Kurt BoonenImmuneSpec, Niel, Belgium.
Sofie PattynIQVIA In vitro Immunology, Charleroi, Belgium.
Elise PepermansImmuneSpec, Niel, Belgium. elise@immunespec.com.
Zuben E SaunaDivision of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. zuben.sauna@fda.hhs.gov.ORCID 0000-0001-8202-5188

Funding

U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration) Intramural
6 · The paper itself

Abstract

Cas9 proteins are derived from human pathogens and are immunogenic, thereby raising potential safety concerns and limiting clinical effectiveness when using Cas9 as a gene-editing tool. Cas orthologs developed from organisms not directly associated with human infections may thus be safer. Here we compare the immunogenicity risk of SaCas9 (derived from the human pathogen, Staphylococcus aureus), AsCas12a (derived from the human commensal, Acidaminococcus sp.) and CasΦ (derived from a bacteria phage, Biggiephage). Ex vivo and in vitro analyses show that SaCas9, AsCas12a and CasΦ are recognized similarly by antibodies and T cells from unimmunized individuals. Using mass-spectrometry to identify MHC-I-bound peptides, we find SaCas9, AsCas12a and CasΦ peptides presented on 9 MHC-I proteins commonly found in the North American population. Our results thus indicate that AsCas12a and CasΦ do not present a less immunogenic alternative to Cas9, and underscore the need for systematic immunogenicity evaluation of all Cas proteins intended for clinical use.

Indexed as

AntibodiesBacterial ProteinsT-LymphocytesHistocompatibility Antigens Class IHumansPeptidesStaphylococcus aureusAntibodiesBacterial ProteinsHistocompatibility Antigens Class IPeptides

Identifiers

PMID42386761
PMCPMC13457614

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.